Toxicity Reduction by (and Hepatoprotective Effects of) Carboxymethyl Pachymaran on 5-Fluorouracil-induced Liver Injury in Mice
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Abstract:
A mouse model of 5-Fu-induced liver injury was established, and peripheral-blood white blood cells (WBC), bone marrow nucleated cells (BMNC), visceral indexes, and alanine transaminase (ALT) and aspartate aminotransferase (AST) activities in serum were quantified after the drug was administered. The effects of CMP on mouse liver tissues were examined using histopathological sectioning of the liver tissues; protein expression levels of Keap1, Nrf2, GCL, NF-κB, p38, pp38, Bax, and Bcl-2 in liver tissues were measured by western blotting; and protein expression levels of NF-κB and pp38 were analyzed by immunohistochemistry. The results showed that compared with the normal group, 5-Fu increased the liver index, spleen index, ALT activity, and AST activity by 13.75%, 53.76%, 39.48%, and 62.81%, respectively. WBC and BMNC values were decreased by 7.15% and 50.81%, respectively; the expression levels of NF-κB, pp38, and Bax in liver tissues were significantly increased, but the expression level of Bcl-2 was decreased, indicating that the liver injury model was successfully established. The CMP treatment of this model decreased the liver index, spleen index, ALT activity, and AST activity by 12.40%, 31.45%, 20.83%, and 20.14%, respectively. WBC and BMNC values were increased by 17.12% and 46.77%, respectively. The expression level of Bcl-2 was significantly increased, while the expression levels of NF-κB, pp38, and Bax were reduced. CMP alone had no significant effect on the liver of normal mice, but effectively reduced the toxicity of 5-Fu and showed apparent hepatoprotective effects. The underlying mechanism is related to the regulation of NF-κB, p38 MAPK, and Bcl-2 signaling pathways.
